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Étude de la réversion du phénotype de Multi Drug Resistance (MDR) par de nouveaux dérivés stéroïdiens, in vitro sur des lignées cellulaires humaines et murines résistantes et in vivo par xénogreffes

Abstract : The chemoresistance of cancer is characterized by a pleitropic resistance to multiple drugs. This mechanism is partly caused by the overexpression of “ATP Binding Cassette” transporters (Pgp, MRP1, BCRP…). Known inhibitors of these transporters such as cyclosporin A, verapamil and RU486 rather toxic at high doses. In this study, many steroid derivatives synthesized in the laboratory (from progesterone or bile acid precursor) to bind and inhibit ABC transporters, specifically the transport by Pgp or BCRP. Several of these synthetic derivatives were able to completely restore the sensivity of the resistant cells compared to cysclosporine A in vitro. In addition, the efficient of these derivatives could, in vivo significantly reduce tumor growth of xenografts on mice and increase survival time of mice. This study opens a route for development of new steroid derivatives with low toxicity, having the ability to reverse the MDR phenotype and restore sensitivity of cancer cells to the chemotherapeutic agents use, with a perspective at clinical use
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https://tel.archives-ouvertes.fr/tel-00877481
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Submitted on : Tuesday, October 29, 2013 - 3:31:10 PM
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Ghina Alame. Étude de la réversion du phénotype de Multi Drug Resistance (MDR) par de nouveaux dérivés stéroïdiens, in vitro sur des lignées cellulaires humaines et murines résistantes et in vivo par xénogreffes. Médecine humaine et pathologie. Université Claude Bernard - Lyon I, 2009. Français. ⟨NNT : 2009LYO10223⟩. ⟨tel-00877481⟩

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